The first and major portion of the proposed project seeks to establish the clinical and functional implications of the high levels of histaminase activity in medullary thyroid carcinoma, & small cell carcinoma of lung. Plasma and tumor tissues from patients with various malignancies will be examined to assess the frequency with which histaminase is associated with certain types of neoplasms. Histaminase will be purified from human pregnancy plasma, human placenta, medullary thyroid carcinoma, and oat cell carcinoma by a new affinity chromatography technique. The molecular species of enzyme will be identified from each tissue source (according to electrophoretic mobility, molecular weight, amino acid content, substrate specificity, and response to inhibitors) in an attempt to identify whether the presence of the enzyme in the tumor tissues represents a placental marker, or whether an enzyme form characteristic of neural crest neoplasms is present. Clinical studies will be ongoing to determine the prognostic significance of high histaminase levels in patients with neural crest tumors, and whether the enzyme activity can be used as a marker to follow the effects of therapy. A second portion of the work seeks to initiate studies to establish the functional significance between biogenic amine production and peptide hormone release by neural crest tumors and normal endocrine tissues. The in vivo and in vitro effects of blockade of biogenic amine synthesis, and metabolism on calcitonin release from medullary thyroid carcinoma, and insulin release from pancreas will be explored. Methods to be employed: 1) Affinity chromatography protein purification; 2) gel electrophoresis; 3) amino acid analysis; 4) radioassays of enzyme activity; 5) radioimmunoassays of peptide hormone; 6) tissue culture of tumor cells.